Current genetic screening guidelines overlook most cases of familial hypercholesterolemia

Current genetic screening guidelines fail to identify most people with an inherited condition known as familial hypercholesterolemia that can cause dangerously high cholesterol and early heart disease, a Mayo Clinic study found. 

The condition often passes silently through families for generations. It is highly treatable, yet people who remain undiagnosed are at greater risk for heart attacks and strokes. 

Cardiovascular disease remains the leading cause of death in the United States, affecting millions of adults each year. It includes conditions such as coronary artery disease, heart failure and stroke. One of its key risk factors is high cholesterol. 

The study, published in Circulation: Genomic and Precision Medicine, suggests that routine screening could identify the majority of people with the inherited condition and, ultimately, save lives. 

Study reveals missed diagnoses 

Researchers found that nearly 90% of those with familial hypercholesterolemia would not have been flagged for standard genetic testing and were unaware they had the condition until DNA testing in a Mayo Clinic population-based research study identified them. About 1 in 5 had already developed coronary artery disease. 

Our findings expose a blind spot in current national guidelines, which rely on cholesterol levels and family history to determine who should receive genetic testing. If we can find those at risk of cardiovascular disease early, we can treat it early and change its course and likely save lives." 

Niloy Jewel Samadder, M.D., lead author and Mayo Clinic gastroenterologist and cancer geneticist, Mayo Clinic Comprehensive Cancer Center

Familial hypercholesterolemia is one of the most common genetic conditions, affecting an estimated 1 in 200 to 250 people worldwide. It causes very high levels of low-density lipoprotein (LDL) cholesterol - the "bad" cholesterol - from birth.

The study analyzed data from exome sequencing, a form of genetic testing that reads the protein-coding regions of the genome - where most disease-causing variants are found. The research included more than 84,000 participants across Mayo Clinic sites in Arizona, Florida and Minnesota through the Tapestry DNA research study, part of the institution's effort to integrate genomics into everyday patient care. 

The research team identified 419 people with genetic variants known to cause familial hypercholesterolemia. They found that nearly 75% of those individuals would not have met current clinical criteria for genetic testing based on their cholesterol levels or family history. This represents a missed opportunity for disease prevention. 

Integrating genetics into preventive care 

Dr. Samadder says the next step is to bring genetic screening into routine care to identify high-risk patients earlier and start treatment sooner. 

The work is part of Mayo Clinic's Precure strategic priority, which aims to predict and prevent serious diseases before they advance. Through innovative technologies and population-based studies, Precure is designed to bring prevention-focused care directly to patients sooner.